The project, funded by the German Federal Ministry of Education and Research under grant 16LW0054, ran from 1 October 2021 to 30 September 2022 and was led by Prof. Peter Neubauer of the Institute for Biotechnology, Bioengineering at the Technical University of Berlin. The consortium comprised academic partners from the university’s Institute for Chemistry (Prof. Nediljko Budisa) and the Institute for Biotechnology, as well as external collaborators. ConsulTech GmbH was contracted to perform a market analysis, while Dendropharm GmbH supplied a subcontract for formulation development. Additional expertise in medicine, materials science, and business was brought in through external consultants to assess medical requirements and market viability.

Scientifically, the project focused on creating a light‑activated, biosynthetic protein adhesive derived from marine mussel proteins. The adhesive’s production via biotechnological methods is cheaper than extracting proteins from animal or human sources and eliminates the risk of transmitting infectious agents. Photoactivation provides a unique trigger for adhesion, enabling precise control in aqueous environments. The team identified three key advantages of the mussel‑based adhesive over competitors: lower production cost, absence of infectious risk, and the novel photo‑triggered adhesion mechanism.

A major technical challenge addressed was the scale‑up of the production process. Traditional scale‑up can introduce gradients in the liquid phase, impairing synthesis performance and product quality. To mitigate this, the team developed scale‑down concepts that replicate large‑reactor gradients in small‑reactor environments, allowing early detection of scale‑up risks. They also explored the use of shake flasks and 2‑dimensional wave‑mixed single‑use bioreactors (Celltainer®) to eliminate the need for pre‑cultures and reduce transfer phases. The wave‑mixed reactor, available in variants up to 150 L, achieves gas‑transfer rates comparable to stirred‑tank reactors while offering lower capital costs and simplified sterilization.

Process monitoring was enhanced through automated, online/offline methods. Fluorescence microscopy and flow cytometry were employed to assess protein expression and cell viability, respectively. These techniques were integrated into the workflow to provide real‑time data, reducing manual effort and accelerating optimization. The project also engineered a complex medium for an optimized E. coli 895A strain, achieving up to a 30‑fold increase in protein production. Additionally, an E. coli B95M strain devoid of nitroreductases was developed, enabling the incorporation of meta‑ONB‑DOPA without subsequent reduction.

The outcomes were disseminated through national and international conferences, and a scientific journal manuscript was prepared. The project also supported the training of early‑career scientists by supervising several bachelor theses. Overall, the work established a robust platform for producing a photo‑activated mussel‑protein adhesive with scalable, cost‑effective manufacturing processes, setting the stage for the subsequent feasibility phase of the program.